NUB OF THE MATTER

All marketers are confronting daily challenges of slicing through the market.  Most succeed partially, and a handful are declared winner marketers.  How do these winners get made?

The starting point for a winner formula in marketing is KNOWLEDGE.  To know is to win!  The knowledge starting point should be as granular (or even molecular) as it can get.  Swimming through the detailed knowledge throws up insights and ideas.  These get translated into decisions, followed by action plans and then execution.  The output decides if it was a winner approach or a mediocre one.

Is there a strategy for knowledge mining?

Knowledge (practical and theoretical) should arise from the ‘nub of the matter’.  You can call this as the ‘nub-of-the-matter approach to knowledge creation and understanding’.  In the case of developing medicinal molecules, it is normally target molecule centric R and D strategy.  Hence, to develop a knowledge that aids training and marketing, it is judicious to begin with the target molecule and develop knowledge in a nutshell in that vein.  Thus, knowing more about the target molecule responsible for the medicine’s development becomes the “nub of the matter” for developing pharma marketing strategy.

Consider the following example:

Dipeptidyl peptidase 4 enzyme (DPP4): Like all enzymes - this enzyme too is a biocatalyst, and belongs to the family of dipeptidyl peptidase enzymes (EC 3.4.14 classification).  There are many such enzymes in this family – such as, DPP3, DPP6, DPP7, DPP8, DPP 9 etc.  DPP4 is also known as CD26. 

DPP4 AND CANCER:

DPP4 has a wide ranging role in cell metabolism.  DPP4 enzyme can bind with many molecules (proline or alanine containing peptides) like growth factors and neuropeptides.  It is popular among cell biologists as an enzyme, which has association with cancer!  DPP4 enzyme levels are increased in certain cancers and reduced in certain other types of cancers.  DPP4 is marker molecule for various cancerous tumors!

DPP4 AND FIBROSIS:

Fibrosis is development of hard connective fibrous tissue in organs.  Eg., liver fibrosis.  DPP4 has been implicated in fibrosis of various organs (eg., liver and kidney).

DPP4 AND GLUCOSE METABOLISM 

DPP4 is involved in glucose metabolism.  DPP4 degrades or breaksdown molecules that are collectively called as incretins.  The umbrella term incretins refers to a group of metabolic hormones (chemical messengers).  Most accurate examples of incretins are: GLP 1 (glucagon like peptide 1) and GIP (gastric inhibitory peptide).  These two are a part of the glucagon peptide family.  DPP4 breaksdown GLP 1 and GIP.

What do GLP and GIP (the two incretins do?)

GLP 1 and GIP (the two incretins) decrease glucagon blood levels and increase insulin blood levels.

K cells in the intestines secrete GIP and ‘L’ endocrine cells in the intestines secrete GLP 1.

a)      GLP 1 (a 30 amino acid peptide gut hormone)

-          stimulates beta cells in pancreas (Islets of Langerhans) to produce more of the blood glucose lowering hormone: insulin (the chemical messenger in blood that transfers glucose from blood into cells, thus, lowering blood glucose and ensuring glucose for cell energy production)

-          GLP 1 also increases beta cell mass in pancreas

-          GLP 1 inhibits glucagon secretion (thus overall GLP 1 helps in rapid postprandial decrease of blood glucose) (Glucagon is a hormone with opposite effects of insulin.  Thus, glucagon tends to increase blood sugar levels and insulin tends to decrease blood glucose levels.  Glucagon the peptide hormone is released in large quantities when blood glucose levels decrease below normal, glucagon stimulates liver to convert stored glycogen into glucose and this gets into the blood stream)

b)      GIP (a 42 amino acid gut hormone)

-          stimulates release of insulin

-          GIP helps promote growth and survival of beta cells of pancreas

-          GIP has a role in fat and bone metabolism

In a healthy body, the release of  insulin and glucagon from pancreas are in balance.

THUS, WHEN DPP4  proteinaceous enzyme BREAKSDOWN GLP 1 AND GIP - THE TWO INCRETINS; more glucagon is released and less insulin is produced from the pancreas.

WHAT ARE DPP4 INHIBITORS?

DPP4 inhibitors are a class of medicines that inhibit the enzyme DPP4, hence, degradation of incretins is decreased.  This in turn increases levels of the two incretins (GLP 1 and GIP), resulting in

-          decrease of glucagon release from pancreas

-          increase of insulin release from pancreas.

Thereby, DPP4 inhibitors have a hypoglycemic effect (lower the levels of blood glucose) and have application in Type 2 diabetes management.

Examples of DPP4 inhibitor drugs:

Sitagliptin (the first in this class), TENELIGLIPTIN (the most widely prescribed and sold, and most economical gliptin in India.  This is the only gliptin manufactured from API stage to formulation stage in India), saxagliptin, vildagliptin (currently the costliest gliptin in India), alogliptin and lindagliptin

Any side effects of DDPP 4 inhibitors (or incretin enhancers)?: the following may happen in some patients (not all)

-          Statistically significant increase in heart failure (scary?  Remember rofecoxib and pioglitazone controversies?  Sitagliptin the first DPP4 inhibitor was invented by Merck, the same people who invented rofecoxib!!), however, medical literature says there is overall good safety profile for gliptins

-          Diarrhea

-          Increased incidence of URTI (upper respiratory tract infections)

-          Sore throat

DPP4 inhibitors do not increase body weight nor cause hypoglycemic episodes.  Dosage adjustment is not normally required in case of renal stress and hepatic dysfunction.

GIP is also known as glucose dependent insulinotropic polypeptide.

Teneligliptin is a research product of Mitsubishi Tanabe Pharma, Japan and it was launched first in the world by both Tanabe Pharma and Daiichi Sankyo, in Sep 2012! (By the way, Daiichi Sankyo purchased the company Ranbaxy and sold it for a loss to Sun Pharma).  Teneligliptin is sold in Japan, Korea and India, currently.

In India, teneligliptin in Dec 2015 had 16 brands, with sales of Rs. 36 crores, in the Rs. 6000 crores antidiabetic market.  Glenmark has been taking risks and fighting for its share of pie in the hot antidiabetic gliptin market, its first tryst with gliptins being with sitagliptin (first gliptin in India from Merck).  However, Glenmark lost its patent battle for sitagliptin against Merck.  Not to be outdone, Glenmark bounced back into the gliptin market, with the third generation oral gliptin.  Teneligliptin is a hot market – because it has the most players, this is the only gliptin which is not under patent. The other patent protected gliptins: vildagliptin, saxagliptin, linagliptin and sitagliptin are not doing as great as teneligliptin.  So the age old adage, more the players, more the noise and market expansion occurs!  Hence, teneligliptin is the numero uno gliptin in India.  (Ref. for data: Business Standard, dated, 20.11.16, page no. 2).

Marketing of a branded formulation containing teneligliptin (hypothetical example):

On the basis of above target molecule knowledge one can successfully create a messaging campaign.  As is the works, brand name finalization, brand name font, CMYK and B/W colour standardization, brand logo or insignia concept and details, and brand audio signature tune (for digital and audio messaging strategy)…are finalized with brain storming sessions and sorting out the available choices in co-ordination with the design team.

Background:

Brand name: Tenali

Brand positioning statement: Enhances incretins, decreases blood glucose

Brand target audience:

a)      Type 2 diabetes patients (as monotherapy or add on)

b)      Endocrinologists, Consulting Physicians treating diabetes (diabetes specialists) and top GPs

Main brand messaging tools and methods:

a)      For MRs (field personnel): visual aid, leave behind literatures, reminder cards, stickers, eye catching theme based sample cartons, electronic visual aid page for use in tablet/mobile screen and short 60 second video film (mobile phone and tablet compatible)

b)      For medical journals: 1 page advertisement material

(Other marketing parameters in terms of number of target doctors, number of visits per month, courier marketing reminders, permission email marketing, other forms of permission based digital and mobile phone medium marketing, in-clinic activities, in-booth activities, in-pharmacy activities, CME activities and campaigns to be worked out too; based on planned activities suitable collaterals like leave behinds, patient information leaflets, die-cut literatures, reminder cards etc are also created)

Let us assume we also make a simple 1 page print visual aid copy for the teneligliptin brand to get a hang of the messaging concept.  There will, of course, be more visual aid pages highlighting safety, efficacy and utility of drug; however, here is just a one visual aid page sample:

State of art therapy for Type 2 diabetes patients

TENALI (Teneligliptin 20 mg tablets)

Enhances incretins, decreases blood glucose

Ø  Dependably inhibits DPP4 enzyme to decrease degradation of endogenous incretins: GLP 1 and GIP

Ø  Increases levels of GLP 1 and GIP to help restore normoglycemia, by reduced glucagon secretion and increased insulin release from pancreas

Ø  Additionally offers vasoprotection from ‘high blood glucose’ induced oxidative stress

‘Teneligliptin (Tenali) has antioxidant properties, ameliorates oxidative stress…caused by chronic exposure to high blood glucose by blood endothelial cells’ Ref.: Endocrine. 2016 Aug 16.

Recommend STATE OF ART THERAPY IN T2DM

TENALI (Teneligliptin 20 mg tablets)                                                          (PACK SHOT)

Enhances incretins, decreases blood glucose

Detailing story: Dr., season’s greetings, (pause) presenting the state of art therapy for Type 2 diabetes patients.  Please choose to recommend Tenali, teneligliptin 20 mg tablets (pause) enhances incretins, decreases blood glucose.

Tenali dependably inhibits DPP4 enzyme to decrease degradation of endogenous incretins: GLP 1 and GIP

Tenali increases levels of GLP 1 and GIP to help restore normoglycemia, by reduced glucagon secretion and increased insulin release from pancreas

Tenali additionally offers vasoprotection from high blood glucose induced oxidative stress, as per this reference, Tenali Teneligliptin has antioxidant properties, ameliorates oxidative stress…caused by chronic exposure to high blood glucose by blood endothelial cells.

Recommend state of art therapy in type 2 diabetes mellitus, Tenali, teneliglipin 20 mg tablets, enhances incretins, decreases blood glucose.

Above is the NUB OF THE MATTER APPROACH to understanding a drug from target molecule angle, and consequently developing a marketing messaging approach.  Please scroll to read below posts, and also recommend this blog to your acquaintances!  Click on older posts to continue reading.